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  • 1. Adams, D.
    et al.
    Coelho, T.
    Conceicao, I.
    Cruz, M. Waddington
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Ziyadeh, N.
    Partisano, A.
    Chen, J.
    Sweetser, M.
    Gollob, J.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Phase 2 open-label extension (OLE) study of patisiran with or without a TTR stabilizer for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 31-32Article in journal (Other academic)
  • 2.
    Andersen, Peter M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Abrahams, Sharon
    Borasio, Gian D.
    de Carvalho, Mamede
    Chio, Adriano
    Van Damme, Philip
    Hardiman, Orla
    Kollewe, Katja
    Morrison, Karen E.
    Petri, Susanne
    Pradat, Pierre-Francois
    Silani, Vincenzo
    Tomik, Barbara
    Wasner, Maria
    Weber, Markus
    EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS): revised report of an EFNS task force2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 3, p. 360-E24Article in journal (Refereed)
    Abstract [en]

    Background: The evidence base for the diagnosis and management of amyotrophic lateral sclerosis (ALS) is weak. Objectives: To provide evidence-based or expert recommendations for the diagnosis and management of ALS based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were searched, and original papers, meta-analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in February 2011. Recommendations were reached by consensus. Recommendations: Patients with symptoms suggestive of ALS should be assessed as soon as possible by an experienced neurologist. Early diagnosis should be pursued, and investigations, including neurophysiology, performed with a high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives/carers should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted. Percutaneous endoscopic gastrostomy feeding improves nutrition and quality of life, and gastrostomy tubes should be placed before respiratory insufficiency develops. Non-invasive positive-pressure ventilation also improves survival and quality of life. Maintaining the patient's ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end-of-life care should be discussed early with the patient and carers, respecting the patient's social and cultural background.

  • 3.
    Biström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jons, Daniel
    Engdahl, Elin
    Gustafsson, Rasmus
    Huang, Jesse
    Brenner, Nicole
    Butt, Julia
    Alonso-Magdalena, Lucia
    Gunnarsson, Martin
    Vrethem, Magnus
    Bender, Noemi
    Waterboer, Tim
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Olsson, Tomas
    Kockum, Ingrid
    Andersen, Oluf
    Fogdell-Hahn, Anna
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Epstein-Barr virus infection after adolescence and Human herpesvirus 6A as risk factors for multiple sclerosis2021In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 28, no 2, p. 579-586Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Infections with human herpesvirus 6A (HHV‐6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV‐6A associated risks of developing MS.

    Methods:  In this nested case–control study, Swedish biobanks were accessed to find pre‐symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead‐based multiplex assay was used to determine serological response against EBV and HHV‐6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

    Results: Seropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV‐6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).

    Conclusions: This study suggests EBV infection after adolescence and age independent HHV‐6A infection as risk factors for MS.

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  • 4.
    Boremalm, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Juto, A.
    Axelsson, M.
    Novakova, L.
    Frisell, T.
    Svenningsson, A.
    Lycke, J.
    Piehl, F.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis2019In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no 8, p. 1060-1067Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Breakthrough disease on first-line injectables in relapsing-remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.

    Methods: Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder-adjusted Cox proportional hazard models.

    Results: A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2-5.6) for RTX and 3.4 (95% CI, 1.3-9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01-0.38) for RTX and 1.0 (95% CI, 0.6-1.7) for FGL vs. NTZ.

    Conclusions: In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.

  • 5. Brenner, P.
    et al.
    Burkill, S.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm.
    Hillert, J.
    Bahmanyar, S.
    Montgomery, S.
    Multiple sclerosis and risk of attempted and completed suicide - a cohort study2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 8, p. 1329-1336Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Patients with multiple sclerosis (MS) are known to have an elevated suicide risk, but attempted suicide is incompletely investigated. The relation between education level and suicidality has not been investigated in MS patients. Our objective was to estimate attempted suicide and completed suicide risks amongst MS patients.

    Methods: A total of 29 617 Swedish MS patients were identified through the Swedish Patient Register and matched with 296 164 people without MS from the general population. Cox regression analysis estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of MS with attempted and completed suicide, with adjustment for age, sex, education and calendar period.

    Results: The adjusted HR for attempted suicide amongst MS patients is 2.18 (95% CI 1.97-2.43) compared with the general population cohort. For completed suicide the HR is 1.87 (95% CI 1.53-2.30). In both groups women are at higher risk of attempting suicide, whilst men are at higher risk of completing suicide. Education level is inversely associated with completed suicide amongst the non-MS cohort (0.68, 0.51-0.91), but not amongst MS patients (1.10, 0.60-2.04).

    Conclusion: Multiple sclerosis patients are at higher risk of both attempted and completed suicide. No evidence was found of an inverse association between educational level and risk of completed suicide amongst MS patients.

  • 6.
    Breu, Markus
    et al.
    Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
    Sandesjö, Fredrik
    Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Milos, Ruxandra-Iulia
    Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
    Svoboda, Jan
    Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Schneider, Lisa
    Division of Infectious Diseases, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
    Reichelt, Julian Benedikt
    Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; Department of Neurology, Medical University of Vienna, Vienna, Austria.
    Bertolini, Annikki
    Department of Pediatric Neurology, University Witten/Herdecke, Children's Hospital Datteln, Datteln, Germany.
    Blaschek, Astrid
    Paediatric Neurology and Developmental Medicine, Ludwig Maximilian University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany.
    Fink, Katharina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Höftberger, Romana
    Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
    Lycke, Jan
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Rostásy, Kevin
    Department of Pediatric Neurology, University Witten/Herdecke, Children's Hospital Datteln, Datteln, Germany.
    Seidl, Rainer
    Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
    Siegert, Sandy
    Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
    Wickström, Ronny
    Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Kornek, Barbara
    Department of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
    Rituximab treatment in pediatric-onset multiple sclerosis2024In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk–benefit profile of RTX in pediatric-onset multiple sclerosis are scarce.

    Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed.

    Results: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38–0.92) to 0.03 (95% CI 0.02–0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70–2.48) to 0.08 (95% CI 0.03–0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30–3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events.

    Conclusion: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

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  • 7. Burgunder, J-M
    et al.
    Schöls, L
    Baets, J
    Andersen, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Gasser, T
    Szolnoki, Z
    Fontaine, B
    Van Broeckhoven, C
    Di Donato, S
    De Jonghe, P
    Lynch, T
    Mariotti, C
    Spinazzola, A
    Tabrizi, S J
    Tallaksen, C
    Zeviani, M
    Harbo, H F
    Finsterer, J
    EFNS guidelines for the molecular diagnosis of neurogenetic disorders: motoneuron, peripheral nerve and muscle disorders2011In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 18, no 2, p. 207-E20Article in journal (Refereed)
    Abstract [en]

    Objectives: These EFNS guidelines on the molecular diagnosis of motoneuron disorders, neuropathies and myopathies are designed to summarize the possibilities and limitations of molecular genetic techniques and to provide diagnostic criteria for deciding when a molecular diagnostic work-up is indicated. Search strategy: To collect data about planning, conditions and performance of molecular diagnosis of these disorders, a literature search in various electronic databases was carried out and original papers, meta-analyses, review papers and guideline recommendations reviewed. Results: The best level of evidence for genetic testing recommendation (B) can be found for the disorders with specific presentations, including familial amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, Charcot-Marie-Tooth 1A, myotonic dystrophy and Duchenne muscular dystrophy. For a number of less common disorders, a precise description of the phenotype, including the use of immunologic methods in the case of myopathies, is considered as good clinical practice to guide molecular genetic testing. Conclusion: These guidelines are provisional and the future availability of molecular-genetic epidemiological data about the neurogenetic disorders under discussion in this article will allow improved recommendation with an increased level of evidence.

  • 8. de Flon, P.
    et al.
    Kumlien, E.
    Reuterwall, Christina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mattsson, P.
    Empirical evidence of underutilization of referrals for epilepsy surgery evaluation2010In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 17, no 4, p. 619-625Article in journal (Refereed)
    Abstract [en]

    Background: Epilepsy surgery is a treatment that can cure patients with intractable epilepsy. This study investigates whether referrals for epilepsy surgery evaluation are underutilized. Methods: Patients with epilepsy aged 18-60 years were identified in a computerized registry held by public health care providers in a Swedish county using ICD codes. Clinical data and data on referral status for epilepsy surgery were obtained from the patients' medical records. Potential candidates for epilepsy surgery evaluation were identified using pre-specified criteria. Obstacles for referral were analysed by comparing clinical data in patients who were considered for referral and those who were not. Appropriateness of non-referral was evaluated against recommendations from the Swedish Council on Technology in Health Care (SBU). Results: Of 378 patients with epilepsy in the registry, 251 agreed to participate. Of 251, 40 were already referred patients and 48 patients were identified as potential candidates for epilepsy surgery evaluation by study criteria. Referral had been considered but not performed in 15 of the potential candidates. Potential candidates not considered for referral were less likely to have seen a neurologist, to have had an EEG, CT and MRI, and more likely to have cognitive disturbances. Following the recommendations by the SBU, 28 of 48 potential candidates were identified as inappropriately not referred patients. Conclusion: The number of missed referrals for epilepsy surgery evaluation was estimated to be 60 per 100 000 inhabitants. Several important obstacles were found for not referring patients for epilepsy surgery evaluation.

  • 9.
    Domellöf, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Fagard, J.
    Laboratoire psychologie de la Perception,Université Paris Descartes, Paris, France.
    Jacquet, A.-Y.
    Laboratoire Psychologie de la Perception (CNRS UMR 8158), Université Paris Descartes, Paris, France.
    Rönnqvist, Louise
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Goal-directed arm movements in children with fetal alcohol syndrome: a kinematic approach2011In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 18, no 2, p. 312-320Article in journal (Refereed)
    Abstract [en]

    Background: Although many studies have documented deficits in general motor functioning in children with fetal alcohol syndrome (FAS), few have employed detailed measurements to explore the specific nature of such disabilities. This pilot study explores whether three-dimensional (3D) kinematic analysis may generate increased knowledge of the effect of intrauterine alcohol exposure on motor control processes by detecting atypical upper-limb movement pattern specificity in children with FAS relative to typically developing (TD) children. 

    Methods: Left and right arm and head movements during a sequential unimanual goal-directed precision task in a sample of children with FAS and in TD children were registered by an optoelectronic tracking system (ProReflex, Qualisys Inc.). 

    Results: Children with FAS demonstrated evidently poorer task performance compared with TD children. Additionally, analyses of arm movement kinematics revealed atypical spatio-temporal organization in the children with FAS. In general, they exhibited longer arm movement trajectories at both the proximal and distal level, faster velocities at the proximal level but slower at the distal level, and more segmented distal movements. Children with FAS also showed atypically augmented and fast head movements during the task performance. 

    Conclusions: Findings indicate neuromotor deficits and developmental delay in goaldirected arm movements because of prenatal alcohol exposure. It is suggested that 3D kinematic analysis is a valid technique for furthering the understanding of motor control processes in children with FAS/fetal alcohol spectrum disorders. A combination with relevant neuroimaging techniques in future studies would enable a more clear-cut interpretation of how atypical movement patterns relate to underlying brain abnormalities.

  • 10.
    Elgh, Eva
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Domellöf, Magdalena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Edström, Mona
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cognitive function in early Parkinson's disease: a population-based study2009In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 12, p. 1278-1284Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson's disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls.

    METHODS: Patients were identified in a longitudinal population based study of idiopathic non-drug induced parkinsonism. Eighty-eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age- and sex-matched healthy control subjects underwent a comprehensive neuropsychological assessment.

    RESULTS: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in > or =1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with > or =2 cognitive domains affected.

    CONCLUSION: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.

  • 11.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An enigmatic neuropathy at the Swedish House of Parliament in the early 20th century2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 841-841Article in journal (Other academic)
  • 12.
    Granberg Sandlund, M.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diamant, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Quality of care in acute dizziness presentations2019In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no S1, p. 926-926Article in journal (Other academic)
    Abstract [en]

    Background and aims: Dizziness is a common symptom at emergency departments. Studies have shown poor quality of care in acute dizziness presentations, including the overuse of computed tomography (CT) and failure to detect benign causes. This study aims to evaluate whether a management algorithm has improved the quality of care for dizzy patients at Umeå University Hospital, Sweden.

    Methods: This was an interventional study using medical records to collect data for acute dizziness presentations before (period 1, 2012–2014) and after (period 2, 2016-2017) the implementation of a management algorithm (see figure). Outcomes were changes in a set of pre-defined quality markers and health economic effects.

    Results: Total n=2126 and n=1487 acute dizziness presentations were identified in period 1 and 2, respectively. Baseline characteristics were similar. The proportion of patients undergoing Dix-Hallpike testing increased, 20.8% vs. 37.7%, (p<0.01), as did BPPV diagnoses, 7.6% vs. 15.3%, (p<0.01). Hospitalization became less common, 61.5% vs. 47.6% (p<0.01). The proportion undergoing any neuroradiological investigation decreased, 44.8% vs. 36.3% (p<0.01) with a shift from CT to MRI, with unchanged sensitivity for diagnosing cerebrovascular causes. The average cost for the care of one dizzy patient decreased from $2561 during period 1 to $1808 during period 2.

    Conclusion: This study shows how the implementation of a management algorithm for dizzy patients can improve the quality of care and lower the expenses, without an increased number of missed stroke cases.

  • 13.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Jons, Daniel
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gustafsson, Rasmus
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Fogdell-Hahn, Anna
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Huang, Jesse
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Brenner, Nicole
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Butt, Julia
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Bender, Noemi
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Unit of Research, Education and Development Östersund Hospital, Umeå University, Umeå, Sweden.
    Alonso-Magdalena, Lucia
    Department of Neurology, Skåne University Hospital in Malmö/Lund and Institution of Clinical Sciences, Neurology, Lund University, Lund, Sweden.
    Gunnarsson, Martin
    Department of Neurology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Vrethem, Magnus
    Department of Neurology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Bergström, Tomas
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Andersen, Oluf
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Kockum, Ingrid
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Waterboer, Tim
    Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Olsson, Tomas
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Cytomegalovirus seropositivity is associated with reduced risk of multiple sclerosis: a presymptomatic case–control study2021In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 28, no 9, p. 3072-3079Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Epstein–Barr virus (EBV) and human herpesvirus 6A (HHV-6A) are associated with increased risk of multiple sclerosis (MS). Conversely, infection with cytomegalovirus (CMV) has been suggested to reduce the risk of MS but supporting data from presymptomatic studies are lacking. Here, it was sought to increase the understanding of CMV in MS aetiology.

    Methods: A nested case–control study was performed with presymptomatically collected blood samples identified through crosslinkage of MS registries and Swedish biobanks. Serological antibody response against CMV, EBV and HHV-6A was determined using a bead-based multiplex assay. Odds ratio (OR) with 95% confidence interval (CI) for CMV seropositivity as a risk factor for MS was calculated by conditional logistic regression and adjusted for EBV and HHV-6A seropositivity. Potential interactions on the additive scale were analysed by calculating the attributable proportion due to interaction (AP).

    Results: Serum samples from 670 pairs of matched cases and controls were included. CMV seropositivity was associated with a reduced risk for MS (OR = 0.70, 95% CI 0.56–0.88, p = 0.003). Statistical interactions on the additive scale were observed between seronegativity for CMV and seropositivity against HHV-6A (AP 0.34, 95% CI 0.06–0.61) and EBV antigen EBNA-1 (amino acid 385–420) at age 20–39 years (AP 0.37, 95% CI 0.09–0.65).

    Conclusions: Cytomegalovirus seropositivity is associated with a decreased risk for MS. The protective role for CMV infection in MS aetiology is further supported by the interactions between CMV seronegativity and EBV and HHV-6A seropositivity.

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  • 14.
    Grut, Viktor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Biström, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stridh, Pernilla
    Lindam, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine. Unit of Research, Education, and Development, Östersund Hospital, Umeå University, Umeå, Sweden.
    Alonso-Magdalena, Lucia
    Andersen, Oluf
    Jons, Daniel
    Gunnarsson, Martin
    Vrethem, Magnus
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Free vitamin D3 index and vitamin D-binding protein in multiple sclerosis: A presymptomatic case-control study2022In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 29, no 8, p. 2335-2342Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: High levels of 25-hydroxyvitamin D3 (25[OH]D3 ) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D-binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS.

    METHODS: A nested case-control study was performed with presymptomatic serum samples identified through cross-linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3 /DBP) × 103 . MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15-0.91, p for trend across quintiles = 0.04). At age 30-39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15-0.85, p for trend = 0.02).

    CONCLUSIONS: These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.

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  • 15.
    Hallberg, Susanna
    et al.
    Department of Clinical Sciences, Karolinska Institutet, Danderyds Sjukhus, Stockholm, Sweden.
    Evertsson, Björn
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lillvall, Ellen
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Boremalm, Malin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    de Flon, Pierre
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Wang, Yunzhang
    Department of Clinical Sciences, Karolinska Institutet, Danderyds Sjukhus, Stockholm, Sweden.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Lycke, Jan
    Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Fink, Katharina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Frisell, Thomas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Al Nimer, Faiez
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Svenningsson, Anders
    Department of Clinical Sciences, Karolinska Institutet, Danderyds Sjukhus, Stockholm, Sweden.
    Hypogammaglobulinaemia during rituximab treatment in multiple sclerosis: a Swedish cohort study2024In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, article id e16331Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Mechanisms behind hypogammaglobulinaemia during rituximab treatment are poorly understood.

    Methods: In this register-based multi-centre retrospective cohort study of multiple sclerosis (MS) patients in Sweden, 2745 patients from six participating Swedish MS centres were identified via the Swedish MS registry and included between 14 March 2008 and 25 January 2021. The exposure was treatment with at least one dose of rituximab for MS or clinically isolated syndrome, including data on treatment duration and doses. The degree of yearly decrease in immunoglobulin G (IgG) and immunoglobulin M (IgM) levels was evaluated.

    Results: The mean decrease in IgG was 0.27 (95% confidence interval 0.17–0.36) g/L per year on rituximab treatment, slightly less in older patients, and without significant difference between sexes. IgG or IgM below the lower limit of normal (<6.7 or <0.27 g/L) was observed in 8.8% and 8.3% of patients, respectively, as nadir measurements. Six out of 2745 patients (0.2%) developed severe hypogammaglobulinaemia (IgG below 4.0 g/L) during the study period. Time on rituximab and accumulated dose were the main predictors for IgG decrease. Previous treatment with fingolimod and natalizumab, but not teriflunomide, dimethyl fumarate, interferons or glatiramer acetate, were significantly associated with lower baseline IgG levels by 0.80–1.03 g/L, compared with treatment-naïve patients. Switching from dimethyl fumarate or interferons was associated with an additional IgG decline of 0.14–0.19 g/L per year, compared to untreated.

    Conclusions: Accumulated dose and time on rituximab treatment are associated with a modest but significant decline in immunoglobulin levels. Previous MS therapies may influence additional IgG decline.

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  • 16.
    Hariz, Marwan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. UCL Queen Square Institute of Neurology, London, United Kingdom.
    Bronstein, Jeff M.
    Department of Neurology, UCLA David Geffen School of Medicine, CA, Los Angeles, United States.
    Cosgrove, G. Rees
    Neurosurgery Department, The Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States.
    de Bie, Rob M. A.
    Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, Netherlands.
    DeLong, Mahlon R.
    Department of Neurology, Emory University School of Medicine, GA, Atlanta, United States.
    Gross, Robert E.
    Department of Neurosurgery, Emory University School of Medicine, GA, Atlanta, United States.
    Krack, Paul
    Department of Neurology, Inselspital, University Hospital Bern, Bern, Switzerland.
    Krauss, Joachim K.
    Department of Neurosurgery, Medical School Hannover, Hannover, Germany.
    Lang, Anthony E.
    The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital and University of Toronto, ON, Toronto, Canada.
    Lees, Andrew J.
    UCL Queen Square Institute of Neurology, London, United Kingdom.
    Lozano, Andres M.
    Division of Neurosurgery, Department of Surgery, University of Toronto, ON, Toronto, Canada.
    Obeso, José A.
    HM CINAC (Centro Integral de Neurociencias Abarca Campal), Fundación Hospitales de Madrid, HM Hospitales, Hospital Universitario HM Puerta del Sur, Madrid, Spain; Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain; University CEU-San Pablo, Madrid, Spain.
    Schuurman, P. Richard
    Department of Neurosurgery, Amsterdam UMC, Amsterdam, Netherlands.
    Vitek, Jerold L.
    Department of Neurology, University of Minnesota, MN, Minneapolis, United States.
    Concerns about the European Academy's recommendations and guidelines regarding pallidotomy for Parkinson's disease2023In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 30, no 6, p. 1831-1833Article in journal (Other academic)
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  • 17.
    Hariz, Marwan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. UCL Queen Square Institute of Neurology, London, United Kingdom.
    Bronstein, Jeff M.
    Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
    Cosgrove, G. Rees
    Neurosurgery Department at The Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
    de Bie, Rob M. A.
    Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.
    DeLong, Mahlon R.
    Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.
    Gross, Robert E.
    Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA.
    Krack, Paul
    Department of Neurology, Inselspital, University Hospital Bern, Bern, Switzerland.
    Krauss, Joachim K.
    Department of Neurosurgery, Medical School Hannover, Hannover, Germany.
    Lang, Anthony E.
    The Edmond J Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital & University of Toronto, Toronto, Ontario, Canada.
    Lees, Andrew J.
    UCL Queen Square Institute of Neurology, London, United Kingdom.
    Lozano, Andres M.
    Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
    Obeso, José A.
    HM CINAC (Centro Integral de Neurociencias Abarca Campal), Fundación Hospitales de Madrid, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain; Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain; University CEU-San Pablo, Madrid, Spain.
    Schuurman, P. Richard
    Department of Neurosurgery, Amsterdam UMC, Amsterdam, The Netherlands.
    Vitek, Jerrold L.
    Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
    Concerns about the European academy's recommendations and guidelines regarding pallidotomy for Parkinson's disease2022In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Article in journal (Refereed)
  • 18. Holmen, C.
    et al.
    Piehl, F.
    Hillert, J.
    Nilsson, P.
    Dahle, C.
    Feltelius, N.
    Svenningsson, Anders
    Norrlands Universitetssjukhus, Umeå.
    Lycke, J.
    Fagius, J.
    Valentin, F.
    Martin, C.
    Olsson, T.
    The 'Immunomodulation and Multiple Sclerosis Epidemiology' (IMSE) study: a Swedish nationwide pharmaco-epidemiological and genetic study focused on long-term safety and efficacy of natalizumab (Tysabri)2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 751-751Article in journal (Other academic)
  • 19.
    Ingre, Caroline
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Press, R.
    Birve, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mutations in VAPB are relatively frequent in the Swedish population, but not associated with ALS2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 82-82Article in journal (Other academic)
  • 20.
    Jashari, Fisnik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Danderyds Hospital, Karolinska Institute, Stockholm, Sweden.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Carotid plaque echogenicity predicts cerebrovascular symptoms: a systematic review and meta-analysis2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 7, p. 1241-1247Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Many reports have shown an association between hypoechoic (echolucent) carotid atherosclerotic plaques and unstable features. In this meta-analysis our aim was to determine the role of carotid plaque echogenicity in predicting future cerebrovascular (CV) symptoms.

    Methods: Electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to September 2015 were systematically searched. Studies with ultrasound-based characterization of carotid artery plaque echogenicity and its association with focal neurological symptoms of vascular origin were eligible for analysis. In the meta-analysis, heterogeneity was measured usingI2 statistics and publication bias was evaluated using the Begg–Mazumdar test. In addition several comparisons between subgroups were performed.

    Results: Of 1387 identified reports, eight studies with asymptomatic patients and three studies with symptomatic patients were meta-analyzed. Pooled analysis showed an association between echolucent carotid plaques and future CV events in asymptomatic patients [relative risk 2.72 (95% confidence interval 1.86–3.96)] and recurrent symptoms in symptomatic patients [relative risk 2.97 (95% confidence interval 1.85–4.78)]. The association was preserved for all stenosis degrees in asymptomatic patients, whilst patients with echolucent plaques and severe stenosis were at higher risk of future events. Also, computer-assisted methods for assessment of carotid plaque echogenicity and studies analyzing ultrasound data collected after the year 2000 showed better prediction.

    Conclusions: In asymptomatic and symptomatic patients, analysis of carotid plaque echogenicity could identify those at high risk of CV events.

  • 21.
    Jashari, Fisnik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Common carotid intima-media measurements determine distal disease structure and vulnerability2015In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, p. 600-601Article in journal (Other academic)
  • 22.
    Kockum, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lilja-Lund, Otto
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, E. -M
    Rosell, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderström, L.
    Virhammar, J.
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 3, p. 569-576Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Despite the important role of imaging in diagnosing idiopathic normal‐pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.

    Methods: In this prospective, population‐based study of iNPH, 168 individuals (93 females) [mean age 75 (range 66–92) years] underwent computed tomography of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters, i.e. Evans’ index, callosal angle, size of temporal horns, narrow high‐convexity sulci, dilated Sylvian fissures, focally dilated sulci, peri‐ventricular hypodensities and bulging of the lateral ventricular roof.

    Results: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, < 0.001) between the total iNPH Radscale score and clinical symptoms. The inter‐rater agreement for the included radiological parameters was high (intraclass correlation, 0.74–0.97).

    Conclusion: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms should raise suspicion of iNPH, motivating further evaluation for shunt surgery.

  • 23.
    Laurell, Katarina
    et al.
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    Artto, V
    Bendtsen, L
    Hagen, K
    Kallela, M
    Meyer, E Laudon
    Putaala, J
    Tronvik, E
    Zwart, J-A
    Linde, M
    Migrainous infarction: a Nordic multicenter study2011In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 18, no 10, p. 1220-1226Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Migrainous infarction (MI), i.e., an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included <10 cases which make conclusions less valid. This study aimed to describe characteristics and outcome of MI in a larger sample.

    METHODS: We analyzed demographic data, risk factors, migraine medication, stroke localization, symptoms, and outcome in a sample of 33 patients with MI according to second edition of the ICHD criteria collected from seven Nordic headache clinics.

    RESULTS: Amongst 33 patients with MI, there were 20 (61%) women and 13 (39%) men with the median age for stroke of 39 (range 19-76) years. Traditional risk factors for stroke were rare compared with Scandinavian young ischemic stroke populations. During the acute phase, 12 (36%) patients used ergotamines or triptans. Stroke was located in the posterior circulation in 27 (82%) patients and cerebellum was involved in 7 (21%). Except in two patients with brainstem infarctions, the outcome was favorable with total recovery or limited residual symptoms.

    CONCLUSIONS: The prevalence of traditional risk factors was low and the infarctions were predominantly located in posterior circulation territory, supporting theories of migraine specific mechanisms. The outcome was in general favorable.

  • 24.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture2015In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, no 10, p. 1410-1416Article in journal (Refereed)
    Abstract [en]

    Background and purpose: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. Methods: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). Results: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. Conclusions: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

  • 25.
    Loutfi, Ghada
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Pallidal deep brain stimulation in the treatment of Huntington's chorea2014In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, p. 125-125Article in journal (Other academic)
  • 26.
    Masrori, Pegah
    et al.
    Department of Neurology, Neuromuscular Reference Center, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven-University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.
    Ospitalieri, Simona
    Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
    Forsberg, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Moens, Thomas G.
    Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven-University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.
    Poesen, Koen
    Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium; Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
    Race, Valerie
    Laboratory for Molecular Diagnosis, University Hospitals Leuven, Leuven, Belgium.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Thal, Dietmar R.
    Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.
    Van Damme, Philip
    Department of Neurology, Neuromuscular Reference Center, University Hospitals Leuven, Leuven, Belgium; Department of Neurosciences, Experimental Neurology, Leuven Brain Institute, KU Leuven-University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium.
    Respiratory onset of amyotrophic lateral sclerosis in a pregnant woman with a novel SOD1 mutation2022In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 29, no 4, p. 1279-1283Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: With the advent of gene therapies for amyotrophic lateral sclerosis (ALS), the importance of gene testing in ALS is increasing. This will likely lead to the identification of new variants for which the pathogenicity is not established. We aimed to study the pathogenicity of a newly identified variant in superoxide dismutase 1 (SOD1).

    METHODS: Gene testing was performed using Sanger sequencing. SOD1 activity in erythrocytes was measured using spectrophotometry. Postmortem brain and spinal cord sections were stained with antibodies against phospho-TDP-43 and SOD1.

    RESULTS: We identified a novel c.416G>T (p.Gly139Val) mutation in SOD1, which caused a rapidly progressive respiratory onset form of ALS. The mutation resulted in a 50% drop of SOD1 activity. Postmortem examination confirmed the absence of TDP-43 pathology and displayed typical SOD1 inclusions in remaining motor neurons, confirming the pathogenic nature of the mutation.

    CONCLUSIONS: Novel variants of unknown pathogenicity will be identified as a result of a surge in gene testing in people with ALS. An in-depth study of a newly identified p.Gly139Val mutation in SOD1 confirmed the pathogenicity of this mutation. Future patients with this particular mutation should qualify for SOD1 silencing or editing therapies.

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  • 27. Menke, R.
    et al.
    Proudfoot, M.
    Wuu, J.
    Andersen, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Talbot, K.
    Benatar, M.
    Turner, M.
    Altered cerebral functional connectivity in pre-symptomatic individuals at risk for ALS2015In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 22, p. 84-84Article in journal (Other academic)
  • 28.
    Moore, Margaret
    et al.
    Department Experimental Psychology, University of Oxford, Oxford, United Kingdom; Queensland Brain Institute, University of Brisbane, Qld, Brisbane, Australia.
    Milosevich, Elise
    Department Experimental Psychology, University of Oxford, Oxford, United Kingdom.
    Beisteiner, Roland
    Department of Neurology, Medical University of Vienna, Vienna, Austria.
    Bowen, Audrey
    Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance and University of Manchester, Manchester, United Kingdom.
    Checketts, Matthew
    Division of Psychology and Mental Health, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.
    Demeyere, Nele
    Department Experimental Psychology, University of Oxford, Oxford, United Kingdom.
    Fordell, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Godefroy, Olivier
    Department of Neurology and Laboratory of Functional Neurosciences and Pathologies, Amiens University Medical Center, Jules Verne University of Picardy, Amiens, France.
    Laczó, Jan
    Memory Clinic, Department of Neurology, Second Faculty of Medicine and Motol University Hospital, Charles University, Prague, Czech Republic; International Clinical Research Center, St Anne's University Hospital Brno, Brno, Czech Republic.
    Rich, Timothy
    Kessler Foundation, NJ, West Orange, United States; Physical Medicine and Rehabilitation, Rutgers University, NJ, Newark, United States.
    Williams, Lindy
    Cognitive Aging and Impairment Neurosciences Lab, University of South Australia, SA, Adelaide, Australia.
    Woodward-Nutt, Kate
    Research and Innovation, Northern Care Alliance National Health Service Group, Salford, United Kingdom.
    Husain, Masud
    Department Experimental Psychology, University of Oxford, Oxford, United Kingdom; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations2022In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 29, no 9, p. 2596-2606Article, review/survey (Refereed)
    Abstract [en]

    Background and purpose: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments.

    Methods: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations.

    Results: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible.

    Conclusions: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

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  • 29.
    Mousavi, Malahat
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Identification of metabolites as predictive biomarkers for dementia2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 472-472Article in journal (Other academic)
  • 30. Nilipour, Y.
    et al.
    Nafissi, S.
    Tjust, Anton E.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Ravenscroft, G.
    Hossein Nejad Nedai, H.
    Taylor, R. L.
    Varasteh, V.
    Pedrosa Domellöf, Fatima
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Zangi, M.
    Tonekaboni, S. H.
    Olivé, M.
    Kiiski, K.
    Sagath, L.
    Davis, M. R.
    Laing, N. G.
    Tajsharghi, H.
    Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies2018In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Nemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed with NEM, definitive mutations are not identified in the known genes, suggesting that there are other genes involved. This study describes compound heterozygosity for rare variants in ryanodine receptor type 3 (RYR3) gene in one such patient.

    METHODS AND RESULTS: Clinical examination of the patient at 22 years of age revealed a long narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear and subsarcolemmal areas, and within the cytoplasm. No likely pathogenic mutations in known NEM genes were identified. Copy number variation in known NEM genes was excluded by NEM-targeted comparative genomic hybridization array. Next-generation sequencing revealed compound heterozygous missense variants in the RYR3 gene. RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain and cauda equina samples. Immunofluorescence of human skeletal muscle revealed a 'single-row' appearance of RYR3, interspersed between the 'double rows' of ryanodine receptor type 1 (RYR1) at each A-I junction.

    CONCLUSION: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain, and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

  • 31. Novakova, L.
    et al.
    Zetterberg, H.
    Axelsson, M.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Khademi, M.
    Gunnarsson, M.
    Malmestrom, C.
    Svenningsson, A.
    Olsson, T.
    Piehl, F.
    Blennow, K.
    Lycke, J.
    Neurofilament light in serum for monitoring multiple sclerosis: A new quantitative tool for measuring disease activity and therapeutic response2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 577-577Article in journal (Other academic)
  • 32. Pihlstrom, L.
    et al.
    Bjornara, K. -A
    Dizdar, N.
    Fardell, C.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Holmberg, B.
    Larsen, J. P.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nissbrandt, H.
    Tysnes, O. -B
    Dietrichs, E.
    Toft, M.
    A Scandinavian multi-centre study replicates 11 susceptibility loci from genome-wide association studies in Parkinson's disease2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 40-40Article in journal (Other academic)
  • 33.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, A.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 27, p. 14-15Article in journal (Other academic)
  • 34.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Vågberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Clinical Sciences, Danderyd Hospital AB, Karolinska Institutet Danderyd Hospital, Stockholm,Sweden.
    Prevention of post-dural puncture headache: a randomized controlled trial2020In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 27, no 5, p. 871-877Article in journal (Refereed)
    Abstract [en]

    Background and purpose: We investigated 952 subjects undergoing diagnostic lumbar puncture (LP) to study the effects of needle size, needle design and stylet reinsertion on the risk of post‐dural puncture headache (PDPH).

    Methods: This randomized double‐blind study was performed at Umeå University Hospital in Sweden during 2013–2018. Subjects were randomly assigned one of three needles [22 gauge (G) atraumatic, 25G atraumatic and 25G cutting] and stylet reinsertion before needle withdrawal or not. The main outcome measure was PDPH assessed by standardized telephone interview(s) 5 days after the LP, repeated until headache cessation. We used logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CI) for PDPH.

    Results: The mean (SD) age was 51.1 (16.7) years and 53.6% were females. The smaller bore (25G) atraumatic needle incurred a lower risk of headache compared with the larger bore (22G) atraumatic needle [22.0% (69/314) vs. 30.2% (98/324); OR, 0.65; 95% CI, 0.45–0.93] and compared with the cutting needle [32.8% (103/314); OR, 0.58; 95% CI, 0.40–0.82]. Reinserting the stylet before needle withdrawal did not reduce the risk of headache.

    Conclusions: These data suggest that a 25G atraumatic needle is superior to a larger atraumatic needle, and to a same‐sized cutting needle, in preventing PDPH after diagnostic LP. In contrast to one earlier report, this study did not find that stylet reinsertion was effective in preventing PDPH. This study provides class I evidence that a small atraumatic needle decreases the risk of PDPH and that stylet reinsertion does not influence PDPH risk.

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  • 35. Soffietti, R
    et al.
    Baumert, B G
    Bello, L
    von Deimling, A
    Duffau, H
    Frénay, M
    Grisold, W
    Grant, R
    Graus, F
    Hoang-Xuan, K
    Klein, M
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rees, J
    Siegal, T
    Smits, A
    Stupp, R
    Wick, W
    Guidelines on management of low-grade gliomas: report of an EFNS-EANO Task Force.2010In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 17, no 9, p. 1124-1133Article in journal (Refereed)
    Abstract [en]

    WHO classification recognizes grade II astrocytomas, oligodendrogliomas and oligoastrocytomas. Conventional MRI is used for differential diagnosis, guiding surgery, planning radiotherapy and monitoring treatment response. Advanced imaging techniques can increase the diagnostic accuracy. Younger age, normal neurological examination, oligodendroglial histology and 1p loss are favorable prognostic factors. Prophylactic antiepileptic drugs are not useful, whilst there is no evidence that one drug is better than the others. Total/near total resection can improve seizure control, progression-free and overall survival, whilst reducing the risk of malignant transformation. Early post-operative radiotherapy improves progression-free but not overall survival. Low doses of radiation are as effective as high doses and better tolerated. Modern radiotherapy techniques reduce the risk of late cognitive deficits. Chemotherapy can be useful both at recurrence after radiotherapy and as initial treatment after surgery to delay the risk of late neurotoxicity from large-field radiotherapy. Neurocognitive deficits are frequent and can be caused by the tumor itself, tumor-related epilepsy, treatments and psychological distress.

  • 36.
    Suhr, Ole B.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Karayal, O.
    Ericzon, B-G
    Nutritional status and autonomic function in clinical trials of tafamidis for transthyretin familial polyneuropathy2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 775-775Article in journal (Other academic)
  • 37. Sundqvist, E.
    et al.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bomfim, I. Lima
    Hillert, J.
    Alfredsson, L.
    Kockum, I.
    Olsson, T.
    The influence of host genetics on Epstein-Barr virus specific antibody levels in multiple sclerosis patients and controls2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, p. 351-351Article in journal (Other academic)
  • 38.
    Sundström, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Smoke exposure increases the risk for multiple sclerosis.2008In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 15, no 6, p. 579-583Article in journal (Refereed)
    Abstract [en]

    Purpose and methods: To estimate the effect of exposure to smoking on the risk for multiple sclerosis (MS), we analyzed nicotine metabolite (cotinine) levels in biobank samples from 109 MS cases and 218 matched referents.

    Results: Elevated cotinine levels, even modest elevations, were associated with an increased risk for MS (all other categories versus lowest: OR = 2.9; 95% CI: 1.3–6.3). A similar but non-significant risk increase was observed also in the small subset of individuals with samples collected before the onset of MS (all other categories versus lowest: OR = 2.4; 95% CI: 0.26–21). Elevated cotinine was associated with an increased risk for MS predominantly in women (all other categories versus lowest category: OR = 3.9; 95% CI: 1.3–12), whereas the risk increase in men was smaller and non-significant.

    Discussion: Smoke exposure is associated with a higher risk for MS than previously estimated. There seems to be a threshold effect present in the lower range of cotinine in its relation to MS. Modestly elevated cotinine levels suggestive of passive smoking are associated with an increased risk for MS. Smoke exposure may explain the higher incidence of MS in women. These preliminary findings need to be confirmed in an expanded material of prospectively collected samples.

     

  • 39.
    Unéus, Erica
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wilhelmsson, Christer
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wixner, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Åhlström Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Sundström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Visualisation of amyloid deposition within the brain of long-term hereditary transthyretin amyloidosis survivors by 18F-flutemetamol positron emission tomography2019In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 26, no S1, p. 287-287, article id EPR3027Article in journal (Other academic)
    Abstract [en]

    Background and aims: Hereditary transthyretin amyloid (ATTRv) amyloidosis caused by the transthyretin (TTR) Val30Met (p.V50M) mutation is characterised by peripheral neuropathy, and central nervous (CNS) complications has rarely been reported. However, liver transplantation has prolonged the patients’ survival, and CNS complications attributed to amyloid angiopathy caused by CNS synthesis of variant TTR have been reported. The aim of the study was to ascertain CNS amyloid deposition in long-term ATTRv survivors.

    Methods: 20 ATTR Val30Met patients with symptoms from the CNS and a median disease duration of 16 years (9-25 years) together with five Alzheimer (AD) patients, who served as positive controls were included in the study. Amyloid CNS deposits were assessed by 18F- flutemetamol PET/CT examination utilising relative z scores with pons as reference.

    Results: Expectedly, all Alzheimer patients had an clearly increased global composite z score above 2.0 compared with 55% of the ATTRv patients. There was an increased local uptake corresponding to cerebellum in 12 ATTRv patients compared to only one in the AD group (fig 1). Four of these ATTRv patients had a global composite z score within the normal range. No correlation between duration after 9 years and amyloid CNS deposition was noted.

    Conclusion: Amyloid deposition within the brain after long-standing ATTRv amyloidosis is increased and is often noted in the cerebellum. However, not all patient display amyloid CNS deposition, thus, additional causes for CNS complications should always be considered.

  • 40. Valadas, A.
    et al.
    Contarino, M-F
    Albanese, A.
    Bhatia, K. P.
    Falup-Pecurariu, C.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Friedman, A.
    Giladi, N.
    Hutchinson, M.
    Kostic, V. S.
    Krauss, J. K.
    Lokkegaard, A.
    Marti, M. J.
    Milanov, I.
    Pirtosek, Z.
    Relja, M.
    Skorvanek, M.
    Stamelou, M.
    Stepens, A.
    Tamas, G.
    Taravari, A.
    Tzoulis, C.
    Vandenberghe, W.
    Vidailhet, M.
    Ferreira, J. J.
    Tijssen, M. A.
    Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes2016In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 23, no 4, p. 772-779Article in journal (Refereed)
    Abstract [en]

    Background and purposeDystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. MethodsA survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. ResultsLack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. ConclusionsInternationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.

  • 41.
    Van Damme, Philip
    et al.
    Department of Neurology, University Hospitals Leuven, Department of Neuroscience KU Leuven, Center for Brain & Disease Research VIB, Leuven, Belgium.
    Al-Chalabi, Ammar
    Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Chiò, Adriano
    Rita Levi Montalcini Department of Neuroscience, University of Turin, Turin, Italy; Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
    Couratier, Philippe
    Centre SLA, CHU Limoges, Limoges, France.
    De Carvalho, Mamede
    Faculdade de Medicina, Instituto de Medicina Molecular, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal.
    Hardiman, Orla
    Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
    Kuźma-Kozakiewicz, Magdalena
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
    Ludolph, Albert
    Department of Neurology, Ulm University, German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.
    McDermott, Christopher J.
    Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom.
    Mora, Jesus S.
    ALS Unit, Department of Neurology, Hospital Universitario San Rafael, Madrid, Spain.
    Petri, Susanne
    Department of Neurology, Hannover Medical School, Hannover, Germany.
    Probyn, Katrin
    Cochrane Response, London, United Kingdom.
    Reviers, Evy
    EUpALS (European Organization for Professionals and Patients with ALS) and ALS Liga België, Leuven, Belgium.
    Salachas, François
    Neurology Department, Paris ALS Center, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France.
    Silani, Vincenzo
    Department of Neuroscience and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
    Tysnes, Ole-Bjørn
    Department of Neurology, Haukeland University Hospital, Bergen, Norway.
    van den Berg, Leonard H.
    Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands.
    Villanueva, Gemma
    Cochrane Response, London, United Kingdom.
    Weber, Markus
    Neuromuscular Diseases Unit/ALS Clinic, St. Gallen, Switzerland.
    European academy of neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European reference network for neuromuscular diseases (ERN EURO-NMD)2024In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331Article in journal (Refereed)
    Abstract [en]

    Background: This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Organization for Professionals and Patients with ALS (EUpALS).

    Methods: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the effectiveness of interventions for ALS. Two systematic reviewers from Cochrane Response supported the guideline panel. The working group identified a total of 26 research questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available.

    Results: A guideline mapping effort revealed only one other ALS guideline that used GRADE methodology (a National Institute for Health and Care Excellence [NICE] guideline). The available evidence was scarce for many research questions. Of the 26 research questions evaluated, the NICE recommendations could be adapted for 8 questions. Other recommendations required updates of existing systematic reviews or de novo reviews. Recommendations were made on currently available disease-modifying treatments, multidisciplinary care, nutritional and respiratory support, communication aids, psychological support, treatments for common ALS symptoms (e.g., muscle cramps, spasticity, pseudobulbar affect, thick mucus, sialorrhea, pain), and end-of-life management.

    Conclusions: This update of the guideline using GRADE methodology provides a framework for the management of ALS. The treatment landscape is changing rapidly, and further updates will be prepared when additional evidence becomes available.

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  • 42. Virhammar, J
    et al.
    Cesarini, K G
    Laurell, Katarina
    Department of Neuroscience, Uppsala University Hospital, Uppsala, Sweden.
    The CSF tap test in normal pressure hydrocephalus: evaluation time, reliability and the influence of pain2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no 2, p. 271-276Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The cerebrospinal fluid tap test (TT) is a diagnostic tool used to select patients with idiopathic normal pressure hydrocephalus (iNPH) for shunt surgery. The procedure and the evaluation of the TT vary between centres. We aimed to describe the evaluation time after the TT, to assess the variability between repeated measurements, the interrater agreement of the gait tests chosen and finally to investigate whether pain affects the gait performance post-TT.

    METHODS: Forty patients (21 men and 19 women) under evaluation for iNPH underwent a TT. Standardized gait analyses were performed before and 2, 4, 6, 8 and 24 h after the TT and repeated twice on every occasion. Independent of each other, two investigators evaluated the quality of gait. At each assessment time, the patients graded headache and back pain on a visual analogue scale.

    RESULTS: Twenty-seven patients (15 men and 12 women) responded to TT. Improvements in gait speed and number of steps were significant at every assessment time post-TT. The variability between two measurements was low (Intra class correlation coefficient=0.97), and the inter-rater agreement was good with a κ=0.74. Pain correlated negatively with improvement in gait speed (r=-0.40, P<0.05).

    CONCLUSIONS: We suggest that the TT can be evaluated at any time within the first 24 h and should be repeated if the patient does not initially improve. Gait analysis appears reliable between two evaluators. Further, it is indicated that post-lumbar puncture pain negatively affects the gait and should be minimized.

  • 43. Waibel, S.
    et al.
    Neumann, M.
    Rosenbohm, A.
    Birve, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Volk, A. E.
    Weishaupt, J. H.
    Meyer, T.
    Mueller, U.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ludolph, A. C.
    Truncating mutations in FUS/TLS give rise to a more aggressive ALS-phenotype than missense mutations: a clinico-genetic study in Germany2013In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 20, no 3, p. 540-546Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Mutations in the FUS/TLS have been associated with amyotrophic lateral sclerosis (ALS) in a few percent of patients. Methods: We screened 184 familial (FALS) and 200 sporadic German patients with ALS for FUS/TLS mutations by sequence analysis of exons 5, 6 and 13-15. We compared the phenotypes of patients with different FUS/TLS mutations. Results: We identified three missense mutations p.K510R, p.R514G, p.R521H, and the two truncating mutations p.R495X and p.G478LfsX23 in samples from eight pedigrees. Both truncating mutations were associated with young onset and very aggressive disease courses, whereas the p.R521H, p.R514G and in particular the p. K510R mutation showed a milder phenotype with disease durations ranging from 3 years to more than 26 years, the longest reported for a patient with a FUS/TLS mutation. Also, in a pair of monozygous twins with the p.K510R mutation, a remarkable similar disease course was observed. Conclusions: Mutations in FUS/TLS account for 8.7% (16 of 184) of FALS in Germany. This is a higher prevalence than reported from other countries. Truncating FUS/TLS mutations result in a more severe phenotype than most missense mutations. The wide phenotypic differences have implications for genetic counselling.

  • 44.
    Wang, R.
    et al.
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden.
    Fratiglioni, L.
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden and Stockholm Gerontology Research Center, Stockholm, Sweden.
    Laveskog, A.
    Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, KI, Stockholm, Sweden.
    Kalpouzos, G.
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden.
    Ehrenkrona, C-H
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden.
    Zhang, Y.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bronge, L.
    Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, KI, Stockholm, Sweden.
    Wahlund, L-O
    Division of Clinical Geriatrics, NVS, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Bäckman, L.
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden and Stockholm Gerontology Research Center, Stockholm, Sweden.
    Qiu, C.
    Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) − Stockholm University, Stockholm, Sweden.
    Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age?: A population-based study2014In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, no 8, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    Background and purpose:

    White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-epsilon 4 allele.

    Methods:

    This population-based study included 492 participants (age >= 60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models. Results: More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-epsilon 4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-epsilon 4 had no influential effect.

    Conclusion:

    The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-epsilon 4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.

  • 45. Warnke, C.
    et al.
    von Geldern, G.
    Markwerth, P.
    Dehmel, T.
    Hoepner, R.
    Gold, R.
    Pawlita, M.
    Kuempfel, T.
    Maeurer, M.
    Stangel, M.
    Wegner, F.
    Hohlfeld, R.
    Straeten, V.
    Limmroth, V.
    Weber, T.
    Hermsen, D.
    Kleinschnitz, C.
    Hartung, H. -P
    Wattjes, M. P.
    Svenningson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Major, E.
    Olsson, T.
    Kieseier, B. C.
    Adams, O.
    The CSF JCV antibody index for diagnosis of natalizumab-associated PML2014In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, p. 59-59Article in journal (Other academic)
  • 46.
    Wilhelm, Kristina R
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Yanamandra, Kiran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Gruden, M A
    P.K. Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Moscow, Russia.
    Zamotin, V
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Malisauskas, M
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Casaite, V
    Department of Molecular Microbiology and Biotechnology, Institute of Biochemistry, Vilnius, Lithuania.
    Darinskas, A
    Institute of Immunology, Vilnius University, Vilnius, Lithuania.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Morozova-Roche, Ludmilla A
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients2007In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 14, no 3, p. 327-334Article in journal (Refereed)
    Abstract [en]

    Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.

1 - 46 of 46
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